A major risk factor for development of NIDDM is impaired glucose tolerance (IGT). Persons with IGT develop diabetes at annual rates of 3.6 to 8.7 %, depending on ethnic group, levels of fasting and post- challenge glycemia, and history of gestational diabetes (GDM). IGT per se is highly associated with cardiovascular disease (CVD) risk factors. IGT and NIDDM share in common insulin resistance and impaired insulin secretion, and it has been suggested that modification of these factors may prevent the development of NIDDM. The DPP is an NIH-sponsored clinical trial to be conducted in 25 centers in the U.S. The principal objective of the DPP is to prevent or delay the development of NIDDM in a cohort of 4000 persons with IGT. Participants aged 25 yrs and older will be recruited from groups at high risk for NIDDM (eg, obesity or history of GDM). Approximately 50% of participants will be from minority populations including African Americans, Hispanic Americans, Asian and Pacific Island Americans, and Native Americans. Eligibility requirements include a fasting plasma glucose between 100 and 139 mg/dl and a 2-h plasma glucose concentration following a 75-gm oral glucose tolerance test between 140 and 199 mg/dl. The randomized interventions will include: a) intensive lifestyle modification to achieve at least a 7% reduction in body weight and a calorie expenditure of 700 kcal/week through moderate exercise, or b) a standard diet and exercise plan combined with either metformin, troglitazone, or placebo. The primary outcome (NIDDM based on WHO criteria) and secondary outcomes (eg, CVD, lipids, body anthropometry, insulin sensitivity and secretion, and carotid wall thickness) will be compared between groups by intention- to-treat analyses over a median 4.5-yr study duration.